tbuckley/cabot-search huggingface dataset:
Plant Protein‐Peptide Supramolecular Polymers with Reliable Tissue Adhesion for Surgical Sealing
Authors: Junlian Nie, Yingchuan Sun, Xueliang Cheng, Guang Wen, Xiaohuan Liu, Meng Cheng, Jianwu Zhao, Wen Li
Journal: Advanced Healthcare Materials (2023)

The fusion of protein science and peptide science opens up new frontiers in creating innovative biomaterials. Herein, a new kind of adhesive soft materials based on a natural occurring plant protein and short peptides via a simple co-assembly route are explored. The hydrophobic zein is supercharged by sodium dodecyl sulfate to form a stable protein colloid, which is intended to interact with charge-complementary short peptides via multivalent ionic and hydrogen bonds, forming adhesive materials at macroscopic level. The adhesion performance of the resulting soft materials can be fine-manipulated by customizing the peptide sequences. The adhesive materials can resist over 78 cmH2 O of bursting pressure, which is high enough to meet the sealing requirements of dural defect. Dural sealing and repairing capability of the protein-peptide biomaterials are further identified in rat and rabbit models. In vitro and in vivo assays demonstrate that the protein-peptide adhesive shows excellent anti-swelling property, low cell cytotoxicity, hemocompatibility, and inflammation response. In particular, the protein-peptide supramolecular biomaterials can in vivo dissociate and degrade within two weeks, which can well match with the time-window of the dural repairing. This work underscores the versatility and availability of the supramolecular toolbox in the easy-to-implement fabrication of protein-peptide biomaterials.
Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating
Authors: Mohamad Hamieh, Jorge Mansilla-Soto, Isabelle Rivière, Michel Sadelain
Journal: Cancer Discovery (2023)

Abstract The success of chimeric antigen receptor (CAR) T cells targeting B-cell malignancies propelled the field of synthetic immunology and raised hopes to treat solid tumors in a similar fashion. Antigen escape and the paucity of tumor-restricted CAR targets are recognized challenges to fulfilling this prospect. Recent advances in CAR T cell engineering extend the toolbox of chimeric receptors available to calibrate antigen sensitivity and combine receptors to create adapted tumor-sensing T cells. Emerging engineering strategies to lower the threshold for effective antigen recognition, when needed, and enable composite antigen recognition hold great promise for overcoming tumor heterogeneity and curbing off-tumor toxicities. Significance: Improving the clinical efficacy of CAR T cell therapies will require engineering T cells that overcome heterogeneous and low-abundance target expression while minimizing reactivity to normal tissues. Recent advances in CAR design and logic gating are poised to extend the success of CAR T cell therapies beyond B-cell malignancies.
Association Between Ghrelin and Body Weight Trajectory in Individuals With Anorexia Nervosa
Authors: Youngjung R. Kim, Meghan S. Lauze, Meghan Slattery, Roy H. Perlis, Laura M. Holsen, Lauren Breithaupt, Casey M. Stern, Maurizio Fava, Jennifer J. Thomas, Elizabeth A. Lawson, Madhusmita Misra, Kamryn T. Eddy
Journal: JAMA Network Open (2023)

Importance Individuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown. Objective To examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa. Design, Setting, and Participants This prospective cohort study was conducted between April 1, 2014, and March 31, 2020, in the US. Girls and women aged 10 to 22 years were recruited from the greater Boston area from community and area treatment centers, enrolled, and followed up for 18 months. Statistical analyses were performed between January and August 2022. Exposures Presence or absence of anorexia nervosa and elevations in endogenous ghrelin. Main Outcomes and Measures Changes in age- and sex-standardized body mass index percentiles from baseline to 9- and 18-month follow-up were the main outcomes of interest. Results A total of 68 girls and young women (11 [16%] Asian, 4 [6%] Hispanic or Latina, 51 [75%] White [non–Hispanic or Latina], and 2 [3%] other race or ethnicity), including 35 with anorexia nervosa and 33 healthy controls of similar Tanner stage, were included in this study. Anorexia nervosa and healthy control groups were not statistically different by race and ethnicity, Tanner stage, number completing follow-up visits, and the duration between baseline and follow-up visits. At baseline, individuals with anorexia nervosa were slightly older (median [IQR], 20.1 [18.5-21.0] vs 18.7 [14.7-19.4] years; P = .005), had lower body mass index percentiles (median [IQR], 2.4 [0.3-4.7] vs 52.9 [40.4-68.3]; P &amp;amp;lt; .001), and had elevated circulating ghrelin area under the curve composite index (median [IQR], 1389.4 [1082.5-1646.4] vs 958.5 [743.0-1234.5] pg/mL; P = .003) compared with healthy individuals. In linear mixed-effects regression analyses, baseline ghrelin was associated with prospective weight gain after adjusting for diagnosis, age, race, and duration of follow-up (odds ratio, 2.35; 95% CI, 1.43-3.73; P = .004). Conclusions and Relevance In this cohort study, endogenous ghrelin was associated with longitudinal weight gain in individuals with anorexia nervosa. Further studies are warranted to confirm this result and examine its potential clinical utility in treatment development.
Comparative Effectiveness of Intracranial Pressure Monitoring vs No Monitoring in Severe Penetrating Brain Injury Management
Authors: Ali Mansour, Susan Rowell, Plamena P. Powla, Peleg Horowitz, Fernando D. Goldenberg, Christos Lazaridis
Journal: JAMA Network Open (2023)

Civilian penetrating brain injury (PBI) is associated with high mortality. However, scant literature is available to guide neurocritical care monitoring and management of PBI.To examine the association of intracranial pressure (ICP) monitoring with mortality, intensive care unit (ICU) length of stay (LOS), and dispositional outcomes in patients with severe PBI.This comparative effectiveness research study analyzed data from the Trauma Quality Improvement Program of the National Trauma Data Bank in the US from January 1, 2017, to December 31, 2019. Patients with PBI were identified, and those aged 16 and 60 years who met these inclusion criteria were included: ICU LOS of more than 2 days, Glasgow Coma Scale (GCS) score lower than 9 on arrival and at 24 hours, and Abbreviated Injury Scale score of 3 to 5 for the head region and lower than 3 for other body regions. Patients with bilaterally fixed pupils or incomplete data were excluded. A 1:1 propensity score (PS) matching was used to create a subgroup of patients. Patients were divided into 2 groups: with vs without ICP monitoring. Data analysis was conducted between September and December 2022.Intracranial pressure monitoring vs no monitoring.Outcomes were mortality, rate of withdrawal, ICU LOS, and dispositional outcome. Measures were age, initial systolic blood pressure, initial oxygen saturation level on a pulse oximeter, first-recorded GCS score, GCS score at 24 hours, Abbreviated Injury Scale score, midline shift, and pupillary reactivity.A total of 596 patients (505 males [84.7%]; mean [SD] age, 32.2 [12.3] years) were included, among whom 220 (36.9%) died and 288 (48.3%) had ICP monitoring. The PS matching yielded 466 patients (233 in each group with vs without ICP monitoring). Overall mortality was 35.8%; 72 patients with ICP monitoring (30.9%) died compared with 95 patients (40.8%) without ICP monitoring . Patients with ICP monitoring were more likely to survive (odds ratio [OR], 1.54; 95% CI, 1.05-2.25; P = .03; number needed to treat, 10). No difference in favorable discharge disposition was observed. The PS-weighted analysis included all 596 patients and found that patients with ICP monitoring were more likely to survive than those without (OR, 1.40; 95% CI, 1.10-1.78; P = .005). The E-value for the OR calculated from the PS-matched data set was 1.79. In addition, ICP monitoring vs no monitoring was associated with an increase in median (IQR) ICU LOS (15.0 [8.0-21.0] days vs 7.0 [4.0-12.0] days; P < .001).In this comparative effectiveness research study, PBI management guided by ICP monitoring was associated with decreased mortality and increased ICU LOS, challenging the notion of universally poor outcomes after civilian PBI. Randomized clinical trials that evaluate the efficacy of ICP monitoring in PBI are warranted.
Intranasal delivery of BDNF-loaded small extracellular vesicles for cerebral ischemia therapy
Authors: Xin Zhou, Xiaohui Deng, Mengfan Liu, Meiting He, Wenhui Long, Zhibin Xu, Kun Zhang, Tao Liu, Kwok-Fai So, Qing-Ling Fu, Libing Zhou
Journal: Journal of Controlled Release (2023)

Mesenchymal stem cells (MSCs) have shown promise for the therapy of cerebral ischemia in animal studies and clinical trials, yet their clinical application still faces many challenges. Utilizing small extracellular vesicles (sEVs) may overcome these challenges. In the study, we overexpressed brain-derived neurotrophic factor (BDNF) in cultured MSCs and purified sEVs using anion exchange chromatography. In an ischemic stroke mouse model, sEVs selectively targeted the peri-infarct region after intranasal administration, and BDNF loading enhanced the efficacy of sEVs in improved functional behavior, neural repair indicated by infarct volume reduction, increased neurogenesis, angiogenesis, synaptic plasticity, and fiber preservation, as well as decreased inflammatory-cytokine expression and glial response. Intranasal administration of sEVs and BDNF-sEVs resulted in upregulation of neuroprotection-related genes and downregulation of inflammation-related genes, and BDNF-sEVs treatment activated the BDNF/TrkB signaling in the ischemic brain. Transcriptomic and proteomic analysis of sEVs and BDNF-sEVs disclosed abundant proteins and miRNAs involved in neuroprotection and anti-inflammation, and BDNF-sEVs showed different characteristics from sEVs. In conclusion, intranasal delivery of sEVs-loaded BDNF is a promising alternative strategy for the therapy of cerebral ischemia.
Long-Term Outcomes of Brugada Substrate Ablation: A Report from BRAVO (Brugada Ablation of VF Substrate Ongoing Multicenter Registry)
Authors: Koonlawee Nademanee, Fa-Po Chung, Frederic Sacher, Akihiko Nogami, Hiroshi Nakagawa, Chenyang Jiang, Meleze Hocini, Elijah Behr, Gumpanart Veerakul, Jaap Jan Smit, Arthur A.M. Wilde, Shih-Ann Chen, Kohei Yamashiro, Yuichiro Sakamoto, Itsuro Morishima, Mithilesh K. Das, Apichai Khongphatthanayothin, Saran Vardhanabhuti, Michel Haissaguerre
Journal: Circulation (2023)

Treatment options for high-risk Brugada syndrome (BrS) with recurrent ventricular fibrillation (VF) are limited. Catheter ablation is increasingly performed but a large study with long-term outcome data is lacking. We report the results of the multicenter, international BRAVO (Brugada Ablation of VF Substrate Ongoing Registry) for treatment of high-risk symptomatic BrS. We enrolled 159 patients (median age 42 years; 156 male) with BrS and spontaneous VF in BRAVO; 43 (27%) of them had BrS and early repolarization pattern. All but 5 had an implantable cardioverter-defibrillator for cardiac arrest (n=125) or syncope (n=34). A total of 140 (88%) had experienced numerous implantable cardioverter-defibrillator shocks for spontaneous VF before ablation. All patients underwent a percutaneous epicardial substrate ablation with electroanatomical mapping except for 8 who underwent open-thoracotomy ablation. In all patients, VF/BrS substrates were recorded in the epicardial surface of the right ventricular outflow tract; 45 (29%) patients also had an arrhythmic substrate in the inferior right ventricular epicardium and 3 in the posterior left ventricular epicardium. After a single ablation procedure, 128 of 159 (81%) patients remained free of VF recurrence; this number increased to 153 (96%) after a repeated procedure (mean 1.2±0.5 procedures; median=1), with a mean follow-up period of 48±29 months from the last ablation. VF burden and frequency of shocks decreased significantly from 1.1±2.1 per month before ablation to 0.003±0.14 per month after the last ablation (P<0.0001). The Kaplan-Meier VF-free survival beyond 5 years after the last ablation was 95%. The only variable associated with a VF-free outcome in multivariable analysis was normalization of the type 1 Brugada ECG, both with and without sodium-channel blockade, after the ablation (hazard ratio, 0.078 [95% CI, 0.008 to 0.753]; P=0.0274). There were no arrhythmic or cardiac deaths. Complications included hemopericardium in 4 (2.5%) patients. Ablation treatment is safe and highly effective in preventing VF recurrence in high-risk BrS. Prospective studies are needed to determine whether it can be an alternative treatment to implantable cardioverter-defibrillator implantation for selected patients with BrS. URL: https://www. gov; Unique identifier: NCT04420078.
Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures
Authors: Sofie Meulewaeter, Gust Nuytten, Miffy H.Y. Cheng, Stefaan C. De Smedt, Pieter R. Cullis, Thomas De Beer, Ine Lentacker, Rein Verbeke
Journal: Journal of Controlled Release (2023)
Assessing and Addressing the Well-being of Lesbian, Gay, Bisexual, Transgender, and Gender Nonconforming Younger Adults in China
Authors: Carl G. Streed
Journal: JAMA Network Open (2023)

Shufang Sun, PhD; Shicun Xu, PhD; Arryn Guy, PhD; John Guigayoma, MPH; Yanwen Zhang, MSc; Yuanyuan Wang, PhD; Don Operario, PhD; Runsen Chen, PhD
Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis
Authors: Yan Qin, Yanling Liu, Xiaoyun Xiang, Xingqing Long, Zuyuan Chen, Xiaoliang Huang, Jianrong Yang, Wei Li
Journal: Molecular Cancer (2023)

Abstract Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.
Molecular and Clinical Spectrum of Primary Hyperparathyroidism
Authors: Smita Jha, William F Simonds
Journal: Endocrine Reviews (2023)

Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT that may be associated with extraparathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multiglandular disease, recurrent PHPT, young onset PHPT (age ≤40 years), and those with a family history of parathyroid tumors. However, the underlying genetic cause for the majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for the family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy.
Resection of metastases from pancreatic and periampullary nonneuroendocrine tumors.
Authors: I. C. Botwinick, L. Pursell, J. A. Chabot
Journal: Journal of Clinical Oncology (2010)

e14683 Background: The survival benefit from resection of hepatic metastases from colorectal and neuroendocrine tumors has been well documented in the literature. There are limited studies examining the role of metastasectomy in patients with nonneuroendocrine pancreatic or periampullary primary tumors. Methods: We performed a retrospective chart review of 983 patients who underwent resections for pancreatic and periampullary tumors at our institution between 1991 and 2009. Survival was defined in two ways: overall survival was defined as time from primary resection to death or last follow-up, while metastasectomy-survival was defined as time from metastasectomy to death or last follow-up. Results: We identified 15 patients who underwent metastasectomy for nonneuroendocrine tumors, including adenocarcinoma (n = 14) and acinar cell carcinoma (n = 1). The majority of patients underwent resection of hepatic metastases (n = 9), followed by lung (n = 3) and ovarian (n = 3) metastases. Four patients had periampullary tumors. Three of the patients underwent metastasectomy at the primary resection, while remaining metastasectomies were performed after the primary resection and restaging. Median overall survival was 36 months (range = 5-143 months). Median metastasectomy-survival was 9 months (range = 3-143 months). 1-year survival from metastasectomy was 37% while 3-year and 5-year survival from metastasectomy were both 15%. In the subgroup of patients with periampullary tumors, median survival was 13 months, 1-year metastasectomy-survival was 50%, and 3-year survival was 25%. The extreme long-term survivor in our data set (143 months) underwent pancreaticoduodenectomy and hepatic resection for periampullary duodenal adenocarcinoma. In the subgroup of patients with nonampullary tumors, median survival was 9 months, 1-year survival was 31%, with no 3-year survivors. Conclusions: Prior studies note that periampullary cancers have a better prognosis than pancreatic cancers. As surgical technique and methods of preoperative staging improve, perioperative morbidity and mortality from metastasectomy procedures may decrease and the potential survival benefit from metastasectomy may outweigh the risks of complications. No significant financial relationships to disclose.
Changes in Hydroxyurea Use Among Youths Enrolled in Medicaid With Sickle Cell Anemia After 2014 Revision of Clinical Guidelines
Authors: Sarah L. Reeves, Hannah K. Peng, Jeffrey J. Wing, Lindsay W. Cogan, Alka Goel, David Anders, Nancy S. Green, Lynda D. Lisabeth, Kevin J. Dombkowski
Journal: JAMA Network Open (2023)

Youths with sickle cell anemia (SCA) are at risk of pain crises, stroke, and early death. Complications can be reduced by the oral disease-modifying medication hydroxyurea, and in 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered to youths aged 9 months and older with SCA regardless of disease severity.To describe changes in hydroxyurea use among youths with SCA before and after release of the National Heart, Lung, and Blood Institute guidelines.This cross-sectional study was conducted using administrative data from 2010 to 2018 from Michigan and New York State (NYS) Medicaid programs. The study population included youths aged 1 to 17 years with SCA enrolled in the Michigan or NYS Medicaid programs for at least 1 year (Michigan: 2010-2018; NYS: 2012-2018). Youths with SCA were identified using validated claims-based definitions. Data were analyzed from June to October 2020.The main outcome was hydroxyurea use characterized as mean annual counts of days' supply of filled hydroxyurea prescriptions. Rates of hydroxyurea use over time were assessed using regression models (Michigan: zero-inflated negative binomial; NYS: negative binomial). Models included indicators for periods before and after guideline release.A total of 4302 youths with SCA (2236 males [52.0%]; 2676 born 2005-2017 [62.2%]; 150 Hispanic [3.5%], 2929 non-Hispanic Black [68.0%], and 389 non-Hispanic White [9.0%]) contributed 12 565 person-years. The mean (SD) annual days' supply of hydroxyurea was 47.2 (93.6) days per youth in Michigan and 97.4 (137.0) days per youth in NYS. In Michigan, there was an increase in the odds of having nonzero days' supply after the guidelines were released (odds ratio, 1.52; 95% CI, 1.07-2.14). In NYS, no change was seen in the mean days' supply of filled hydroxyurea.These findings suggest that hydroxyurea was substantially underused among youths with SCA, despite establishment as the primary disease-modifying therapy for SCA, and that there was incomplete clinician or patient uptake of newly released guidelines. Results suggest that expanding use of hydroxyurea may require a multifaceted approach that includes addressing multiple system- and patient-level barriers.
Corrigendum to “Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma” [Eur Urol 2023]
Authors: Matthew S. Ernst, Vishal Navani, J. Connor Wells, Frede Donskov, Naveen Basappa, Chris Labaki, Sumanta K. Pal, Luis Meza, Lori A. Wood, D. Scott Ernst, Bernadett Szabados, Rana R. McKay, Francis Parnis, Cristina Suarez, Takeshi Yuasa, Aly-Khan Lalani, Ajjai Alva, Georg A. Bjarnason, Toni K. Choueiri, Daniel Y.C. Heng
Journal: European Urology (2023)
Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis
Authors: Girish Hiremath, Lili Sun, Margaret H. Collins, Peter A. Bonis, Nicoleta C. Arva, Kelley E. Capocelli, Mirna Chehade, Carla M. Davis, Gary W. Falk, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, John Leung, Paneez Khoury, Vincent A. Mukkada, Lisa J. Martin, Jonathan M. Spergel, Joshua B. Wechsler, Guang-Yu Yang, Seema S. Aceves, Glenn T. Furuta, Marc.E. Rothenberg, Tatsuki Koyama, Evan S. Dellon
Journal: Clinical Gastroenterology and Hepatology (2023)
Epigenomic Blood-Based Early Detection of Pancreatic Cancer Employing Cell-Free DNA
Authors: David Haan, Anna Bergamaschi, Verena Friedl, Gulfem D Guler, Yuhong Ning, Roman Reggiardo, Michael Kesling, Micah Collins, Bill Gibb, Kyle Hazen, Steve Bates, Michael Antoine, Carolina Fraire, Vanessa Lopez, Roger Malta, Maryam Nabiyouni, Albert Nguyen, Tierney Phillips, Michael Riviere, Anna Leighton, Christopher Ellison, Erin McCarthy, Aaron Scott, Lauren Gigliotti, Eric Nilson, Judith Sheard, Melissa Peters, Kelly Bethel, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy
Journal: Clinical Gastroenterology and Hepatology (2023)